Genetic aspects of breathing: on interactions between hypercapnia and hypoxia

Indeed, specific genes in humans and mice regulate breathing pattern at baseline and breathing control during chemical stimulation. The current review addresses the question of coupling plausible candidate genes to physiological variation in control of breathing. That is, can genes discovered in mice be candidates assigned to similar physiological mechanisms as genetic control of breathing in humans? As an illustration, this review examines the interaction of hypoxia in affecting the hypercapnic ventilatory sensitivity (HCVS) curve in humans and mice. Strain distribution patterns (SDPs) incorporating ten inbred mouse strains demonstrate that hypoxic stimulation likely influences HVCS via an additive mechanism rather than synergy between hypercapnia and hypoxia (i.e. CO2 potentiation). As a mechanism associated with the chemical control of breathing in humans, the absence Of CO2 potentiation in mice suggests that specific genes interact to establish variation in complex breathing traits among mouse strains and between species. If future studies support the current evidence, the absence Of CO2 potentiation in mice compared with humans suggest a clearly defined species difference, which may depend on alternative hypoxic interactions such as hypometabolic and central neuronal depressive mechanisms in mice. Because the complexity of breathing mechanisms varies with modest adjustments in the environment, gene-targeting strategies that achieve 'one-gene, one-phenotype' results must be complimented with alternative strategies that consider integrating complex respiratory mechanisms with gene-to-gene interactions. (C) 2003 Elsevier Science B.V. All rights reserved.